Multi-reoperations for lung metastases.

In this study, we investigated role and results of multi-reoperations for lung metastases. From 1986 to 2010, 113 consecutive patients (61 men and 52 women; mean age: 53.2 ± 12.8 years) underwent repeated lung metastasectomy with curative intent in our institution. Two procedures were performed in 113 patients, three in 54, four in 31, five in eight and six in three. There was no perioperative mortality. Cumulative 5-year survival was 65% and this was significantly higher than the value recorded for patients undergoing only one metastasectomy (42%; p = 0.021). Size, number of resections and probability of recurrence increased by number of operation whereas disease free interval reduced. At any metastasectomy both short disease-free interval and multiple metastases resulted in the most significant negative prognosticators. In conclusion, redo metastasectomy is worthwhile for the initial procedures, afterwards both disease-free and overall survivals decrease and surgery lose its efficacy.

Erythrocyte osmotic resistance recovery after lung volume reduction surgery.

OBJECTIVES: Alteration of erythrocyte osmotic resistance, with increment of reticulocytes, is common in emphysema. This fragility is probably due to an altered fatty acid membrane composition from lipid peroxidation, a reaction triggered by the disease-related increment of reactive oxidative species. We analysed the effects of lung volume reduction surgery (LVRS) on this anomaly compared with respiratory rehabilitation (RR) therapy. METHODS: We retrospectively compared 58 male patients with moderate-to-severe emphysema who underwent LVRS with 56 similar patients who underwent standardized RR. Respiratory function parameters, erythrocyte osmotic resistance and antioxidant enzymes levels were evaluated before and 6 months after treatments. RESULTS: Significant improvements in respiratory function, exercise capacity, unsaturated fatty acid content (+10.0%, P = 0.035), erythrocyte osmotic resistance (hyperosmolar resistance -21.0%, P = 0.001; hyposmolar resistance -18.0%, P = 0.007) and erythrocyte antioxidant enzymes [superoxide dismutase (SOD) +60.0%, P < 0.001; glutathione peroxidase +39.0%, P = 0.004 and glutathione reductase +24.5%, P = 0.008] were observed after surgery. In the RR group, we did not find any significant improvements in osmotic resistance, although respiratory and functional parameters were significantly improved. Correlation analysis in the surgical group showed that the reduction in residual volume (RV) significantly correlated the normalization of hyperosmotic (P = 0.019) and hyposmotic resistances (P = 0.006), the decrease in the absolute number of reticulocytes (P = 0.037) and increase in SOD (P < 0.001). CONCLUSIONS: LVRS improved unsaturated fatty acid content, erythrocyte osmotic resistance and levels of erythrocyte antioxidant enzymes compared with RR. Correlations between erythrocyte osmotic resistance and antioxidant intracellular enzymes with RV suggest that reduction in lung hyperinflation with the elimination of inflammatory emphysematous tissue may explain such improvements after surgery.

The impact on quality of life after en-bloc resection for non-small-cell lung cancer involving the chest wall.

BACKGROUND: En-bloc resection for non-small cell lung cancer with chest-wall involvement may achieve a 5-year survival rate higher than 40%, but the impact on postoperative quality of life is not yet known. METHODS: Twenty-six patients undergoing en-bloc lung resections were included. Life quality ratings were assessed through a Short-Form 36 questionnaire preoperatively and at six, 12, 18 and 24 month follow-up visits. The degree of dyspnea, pain level, and flow-volume curves were also obtained at the same time periods. Changes occurring over time were analyzed by means of repeated-measure ANOVA. RESULTS: As a whole, the Physical Component Summary score declined six months postoperatively (P < 0.0001) and failed to improve thereafter. Patients with preoperative Forced Expiratory Volume in one second (FEV1 ), <80% predicted (P = 0.029), resected ribs >2 (P = 0.03), and chest wall defect ≥50 cm2 (P = 0.007) experienced a greater and lasting impairment. Net postoperative decrease in FVC (P = 0.02; r = 0.48) and dyspnea worsening (P = 0.03; r =-043 at six months, P = 0.05; r =-0.39 at 12 months) were also correlated with the extent of physical deterioration, whereas age (P = 0.92), gender (P = 0.51), type of resection (P = 0.71), and adjuvant therapy (P = 0.68) did not. The Physical Component Summary didn't change significantly in patients with high pain levels (VAS >7). The Mental Component Summary score increased slightly at six months, with no difference in any patients' subgroup. CONCLUSIONS: The extent of chest wall resection, preoperative FEV1 , and postoperative decline in FVC were the main indicators of quality of life impairment after en-bloc resection for lung cancer. The impact upon quality of life should be considered in a cost-to-benefit ratio of planning this surgery in suboptimal candidates.

Immune profiling by multiple gene expression analysis in patients at-risk and with type 1 diabetes.

There is a need for biomarkers to monitor the development and progression of type 1 DM. We analyzed mRNA expression levels for granzyme B, perforin, fas ligand, TNF-α, IFN-γ, Foxp3, IL-10, TGF-ß, IL-4, IL-6, IL-17, Activation-induced cytidine deaminase (AID) and Immunoglobulin G gamma chain (IgG) genes in peripheral blood of at-risk, new-onset and long-term type 1 DM , and healthy controls. The majority of the genes were suppressed in long-term type 1 DM compared to controls and new-onset patients. IFN-γ, IL-4 and IL-10 mRNA levels were significantly higher in new-onset compared to at-risk and long-term groups. There was decreased mRNA expression for AID and IgG and up-regulation of IFN-γ with age in controls. Data suggest an overall depressed immunity in long-term type 1 DM. Increased gene expression levels for IFN-γ, IL-4 and IL-10 in new-onset patients from at-risk patients might be used as potential markers for progression of the disease.

New predictors of response to neoadjuvant chemotherapy and survival for invasive thymoma: a retrospective analysis.

BACKGROUND: Cell-cycle protein (p27, p21, and p53) expression can predict response to neoadjuvant chemotherapy and prognosis in some neoplasms. This study evaluated whether these markers could also be effective in invasive thymoma during a multimodality treatment. METHODS: Between 1989 and 2008, 33 patients with invasive thymoma underwent surgical resection after neoadjuvant chemotherapy. Expression of p27, p21, and p53 was assessed using immunohistochemistry in specimens retrieved pre and post chemotherapy. Factors influencing response to neoadjuvant chemotherapy and survival were investigated by univariate and multivariate analysis. Good response was defined as complete disappearance of tumor at imaging or necrosis >90% at pathologic studies. RESULTS: Twelve patients disclosed an imaging good response. Complete resection was possible in 17 patients, 9 of whom had presented imaging good response and 11 of whom had revealed pathologic good response. On univariate analysis both imaging and pathologic poor responses were significantly associated with incomplete resection (P = 0.04 and P = 0.03, respectively) and preneoadjuvant triple combination of p27 low, p21 low, and p53 high expressions (P = 0.001 and P < 0.0001, respectively), the last factor being the only one selected on logistic regression (P = 0.01 and P = 0.005, respectively). Long-term survival analysis was negatively influenced by triple combination of p27, p21, and p53 (P < 0.0001) and incomplete resection (P < 0.0001), which were also selected on Cox's regression (P = 0.004 and P = 0.02, respectively). CONCLUSIONS: The triple combination of p27 low, p21 low, and p53 high expressions was the most significant predictor of imaging and pathologic poor responses to neoadjuvant chemotherapy in invasive thymoma. This combination together with incomplete resection was also the most significant negative predictor of long-term survival.

Variations of inflammatory mediators and alpha1-antitrypsin levels after lung volume reduction surgery for emphysema.

RATIONALE: In emphysema, chronic inflammation, including protease-antiprotease imbalance, is responsible for declining pulmonary function and progressive cachexia. OBJECTIVES: To evaluate variations of inflammatory mediators and alpha(1)-antitrypsin levels after lung volume reduction surgery (LVRS) compared with respiratory rehabilitation. METHODS: A total of 28 patients with moderate to severe emphysema, who underwent video-assisted thoracoscopic LVRS, were compared with 26 similar patients, who refused operation and followed a standardized rehabilitation program, and to a matched healthy group. Respiratory function, body composition, circulating inflammatory mediators, and alpha(1)-antitrypsin levels were evaluated before and 12 months after treatment. Gene expression levels of inflammatory mediators and protease-antiprotease were assessed in emphysematous specimens from 17 operated patients by matching to normal tissue from resection margins. MEASUREMENTS AND MAIN RESULTS: Significant improvements were only obtained after surgery in respiratory function (FEV(1), +25.2%, P < 0.0001; residual volume [RV], -19.5%, P < 0.0001; diffusing lung capacity for carbon monoxide, +3.3%, P < 0.05) and body composition (fat-free mass, +6.5%, P < 0.01; fat mass, +11.9%, P < 0.01), with decrement of circulating inflammatory mediators (TNF-alpha, -22.2%, P < 0.001; IL-6, -24.5%, P < 0.001; IL-8, -20.0%, P < 0.001) and increment of antiprotease levels (alpha(1)-antitrypsin, +27.0%, P < 0.001). Supportive gene expression analysis demonstrated active inflammation and protease hyperactivity in the resected emphysematous tissue. Reduction of TNF-alpha and IL-6 and increment of alpha(1)-antitrypsin levels significantly correlated with reduction of RV (P = 0.03, P = 0.009, and P = 0.001, respectively), and partially with increment of fat-free mass (P = 0.03, P = 0.02, and P = 0.09, respectively). CONCLUSIONS: LVRS significantly reduced circulating inflammatory mediators and increased antiprotease levels over respiratory rehabilitation, also improving respiratory function and nutritional status. Correlations of inflammatory mediators and antiprotease levels with RV and, partly, with body composition suggest that elimination of inflammatory emphysematous tissue may explain clinical improvements after surgery.

Long-term metabolic and hormonal effects of exenatide on islet transplant recipients with allograft dysfunction.

The initial success of islet transplantation (ITx) is followed by graft dysfunction (GDF) and insulin reintroduction. Exenatide, a GLP-1 agonist, increases insulin and decreases glucagon secretion and has potential for beta-cell regeneration. To improve functional islet mass, exenatide treatment was given to ITx recipients with GDF. The objective of this study was to assess metabolic and hormonal effects of exenatide in GDF. In this prospective, single-arm, nonrandomized study, 11 type 1 diabetes recipients of ITx with GDF had HbA1c, weight, insulin requirements, and 5-h mixed meal tolerance test (MMTT; with/without exenatide given before test) at baseline, 3, 6, and 12 months after initiating exenatide treatment. Baseline MMTT showed postprandial hyperglycemia and hyperglucagonemia. Daily exenatide treatment resulted in improved glucose, increased amylin/insulin ratio, and decreased proinsulin/insulin ratio as assessed by MMTT. Glucagon responses remained unchanged. Exenatide administration 1 h before MMTT showed decreased glucagon and glucose at 0 min and attenuation in their postprandial rise. Time-to-peak glucose was delayed, followed by insulin, proinsulin, amylin, and C-peptide, indicating glucose-driven insulin secretion. Five subjects completed 12-month follow-up. Glucose and glucagon suppression responses after MMTT with exenatide were no longer observed. Retrospective 3-month analysis of these subjects revealed higher and sustained glucagon levels that did not suppress as profoundly with exenatide administration, associated with higher glucose levels and increased C-peptide responses. In conclusion, Exenatide suppresses the abnormal postprandial hyperglucagonemia and hyperglycemia observed in GDF. Changes in amylin and proinsulin secretion may reflect more efficient insulin processing. Different degrees of responsiveness to exenatide were identified. These may help guide the clinical management of ITx recipients.

Recurrent intrathoracic thymomas: potential prognostic importance of cell-cycle protein expression.

OBJECTIVE: Recurrent intrathoracic thymomas may have an unpredictable behavior. Cell-cycle protein expression has proven useful in predicting outcome in a variety of neoplasms. We investigated its potential prognostic importance in recurrent intrathoracic thymomas. METHODS: We reviewed the case histories of 25 consecutive patients operated on between 1987 and 2004 for intrathoracic recurrence (7 mediastinal, 18 nonmediastinal) after radical thymomectomy. Complete resection was performed in 14 patients. In the other 11 patients incomplete resection was followed by chemotherapy and radiotherapy. Expression of cell-cycle proteins (p53, p21, and p27) was assessed by immunohistochemistry in specimens retrieved from both initial and recurrent thymomas. Univariate and multivariate analysis for prognostic factors present at the time of the recurrence was performed. RESULTS: Eight of 14 patients who underwent complete resection had a second recurrence after a mean free interval of 20 +/- 9 months, and a new complete resection was reperformed in 4. After incomplete resection, chemotherapy and radiotherapy allowed total remission in 4 subjects and only 1 of these had a second recurrence. Survival after surgery of the recurrence was negatively influenced by incomplete recurrence resection (P = .03), first disease-free interval less than 24 months (P = .03), high p53 (P = .04), low p21 (P = .02), low p27 (P = .003) expressions, and combination of these proteins (p53 high, p21 low, p27 low expression) (P = .0001). Multivariate analysis selected the triple combination of cell-cycle protein expression as the most significant prognostic variable (P = .02, odds ratio = 11.96, 95% confidence interval = 1.39-102.63). CONCLUSIONS: Cell-cycle protein expression, and namely the combination of high p53, low p21, and low p27 expression, may have a potential prognostic importance in recurrent intrathoracic thymomas.

Bilateral thoracoscopic T2 to T3 sympathectomy versus botulinum injection in palmar hyperhidrosis.

BACKGROUND: Bilateral T2 to T3 thoracoscopic sympathectomy and injection of botulinum toxin-A are presently the most effective modalities in the treatment of primary palmar hyperhidrosis. In this study we evaluated comparative merits of the two therapies. METHODS: Patients suffering primary palmar hyperhidrosis were treated by either bilateral T2 to T3 thoracoscopic sympathectomy (n = 68) or by injection of botulinum toxin-A (n = 86). The groups were homogeneous for relevant demographic, physiologic, and clinical data. Quantification of sweat production was performed by Minor's iodine starch and glove tests. Subjective changes were assessed by quality of life questionnaires (Hyperhidrosis, Dermatology Life Quality Index, Short Form-36, Nottingham's Health Profile) and patient's satisfaction self-assessment. A cost comparison between groups was also carried out. RESULTS: No operative mortality or major morbidity was recorded in either group. Minor's test showed a more significant reduction in the surgical group: +94% versus +63% at 6 months and +94% versus +30% at 12 months. Compensatory sweating was significantly greater and long-lasting in the surgical group. All subjective tests improved rapidly and significantly in both groups. After 6 months, results mildly worsened in the surgical group and more significantly in the botulinum group. Patient's satisfaction was initially greater in the botulinum group (p = 0.03), but after 6 months it significantly reversed (p = 0.04). Surgical treatment cost approximately as much as four botulinum treatments. CONCLUSIONS: Thoracoscopic sympathectomy is superior to botulinum toxin-A injection. The greater initial costs and discomfort are offset by a greater reduction in compensatory sweating.

Long-term outcome of thoracoscopic extended thymectomy for nonthymomatous myasthenia gravis.

BACKGROUND: Thoracoscopic thymectomy has shown promise in the integrated management of myasthenia gravis (MG) although there is still scant data on long-term results. The aim of this study was to analyze long-term (>5 years) results of thoracoscopic extended thymectomy in nonthymomatous MG. METHODS: We retrospectively reviewed 32 patients operated on between 1995 and 2003. MG foundation of America clinical classification (MGFA), symptoms' duration, preoperative crisis, anticholinesterase-drugs dosage, steroid use, and acetylcholine receptor antibodies were evaluated in all patients with annual follow-up. Anti-MuSK antibody titer was also assessed at the last follow-up. RESULTS: There were 21 females and 11 males with a median age of 36 years. Ten patients were seronegative for acetylcholine receptor antibodies. Patients in MGFA class I, II, III and IV were 7 (22%), 15 (44%), 9 (28%), 2 (6%) patients, respectively. Median symptoms duration was 11 months. There was no mortality or major morbidity. Median hospital stay was 4.0 days. Ectopic thymic tissue was found in 18 (56%) patients. Median follow-up was 119 months (range 60-156 months). There was no residual thoracic pain. Estimated 10-year remission rate was 50%. At 72 months, 27 (84.3%) patients were improved or in complete remission. At the univariate analysis, shorter duration of symptoms (<12 months) and absence of oropharyngeal involvement were both predictors of response to thymectomy (p<0.02) whereas positivity for anti-MuSK antibody was a predictor of non-response (p=0.0007). CONCLUSIONS: Thoracoscopic extended thymectomy yields satisfactory long-term results in patients with nonthymomatous myasthenia gravis although anti-MuSK positivity correlated with poor response to operation.

Symptomatic and quality of life changes after extrapleural pneumonectomy for malignant pleural mesothelioma.

BACKGROUND: Extrapleural pneumonectomy for malignant pleural mesothelioma is considered an aggressive procedure, but symptomatic and quality of life changes are unknown. METHODS: Between 1997 and 2004, 16 consecutive patients underwent extrapleural pneumonectomy for mesothelioma followed by chemo-radiotherapy. Tumor-related symptoms and quality of life (Short-Form-36 and St. George's questionnaires) were assessed pre, 3, 6, 12, and 24 months postoperatively. RESULTS: Thirty-day postoperative major morbidity was 31% with no mortality. At 3 months postoperatively, dyspnea improved in 10 patients (62%), pain in 12 (75%), cough in 10 (62%), fever in 11 (68%), Karnofsky-index in 10 (62%), Short-Form-36 physical-component-summary in 8, mental-component-summary in 5 and total St. George score in 8 (50%). At 1 year 10 (62%) patients were alive and majority of improved parameters were still stable. Thereafter they usually started to decline. Survival was influenced by nonepithelial histology (P < 0.01) and N2-disease (P < 0.01), which showed to be the only prognosticator at Cox regression (P < 0.0001, Odd ratio 5.4). Among symptomatic variables, a 3-month postoperative Short-Form-36 physical-component-summary above the median value correlated significantly with a better prognosis (P < 0.02). CONCLUSIONS: Extrapleural pneumonectomy may rapidly improve symptoms as well as quality of life, especially in physical domains. Other than biological factors, postoperative Short-Form-36 physical component as well, significantly influenced the prognosis.

Minimization and withdrawal of steroids in pancreas and islet transplantation.

For reducing the corticosteroid (CS)-related side-effects, especially cardiovascular events, CS-sparing protocols have become increasingly common in pancreas transplantation (PT). Lympho-depleting induction antibodies, such as rabbit anti-thymocyte globulin (rATG) or alemtuzumab, have been widely used in successful trials. The results of various CS-sparing protocols combining calcineurin inhibitors (CNI) and mycophenolate or sirolimus, have been mixed for rejection and survival rates. Most of the studies were uncontrolled trials of low-risk patients, therefore the grade of evidence is limited. Large-scale prospective studies with long-term follow up are necessary to assess risks and benefits of CS-sparing regimens in PT before recommending such strategies as standard practice. Islet allo-transplantation for patients with brittle type 1 diabetes mellitus, less invasive and safer procedure than PT, has been attempted since late 1980s, but diabetogenic immunosuppressants at maintenance, mainly CS and high-dose CNI, prevented satisfactory results (10% insulin-independence at 1-year post-transplant). Since 2000, CS-free and CNI-reducing protocols, including more potent induction [daclizumab, OKT3gamma1(ala-ala) anti-CD3 antibody, rATG] and maintenance (sirolimus, mycophenolate) agents, have significantly improved short-term outcomes whereas long-term are still inadequate (from 80% to 20% insulin-independence from 1- to 5-year post-transplant). Main limitations are allo- and autoimmunity, immunosuppression-related islet and systemic toxicity and transplant site unsuitability, which tolerogenic protocols and biotechnological solutions may solve.

Long-term insulin independence and improvement in insulin secretion after supplemental islet infusion under exenatide and etanercept.

BACKGROUND: Progressive graft dysfunction (GDF) and loss of insulin independence (II) have been invariably observed in islet transplant recipients under the "Edmonton protocol." To reestablish II, we performed supplemental islet infusions (SI) in recipients of allogeneic islet transplant alone, displaying GDF. To improve the engraftment and long-term graft function of SI, exenatide (EXN) and etanercept treatment at islet infusion, and long-term EXN treatment were tested in a non-randomized pilot clinical trial. METHODS: Patients with GDF received SI under Edmonton-like immunosuppression with daclizumab induction, either without interventions (SI-control; n=5) or with EXN and etanercept treatment (SI-EXN; n=4). Clinical and metabolic profiles were assessed during 18-month follow-up. RESULTS: Long-term II (18 months) was observed in 100% of SI-EXN and in 20% of SI-control (P=0.04). SI-EXN subjects demonstrated restoration of function better than that seen after initial islet infusions. Comparison of SI-EXN and SI-control groups demonstrated better responses in SI-EXN subjects at 3 months post-SI. During the 18 months of follow-up, function was sustained in the SI-EXN subjects better than in SI-controls. Acute effects of EXN during mixed meal tolerance test and intravenous glucose tolerance test results in improved first and second phase insulin release in response to intravenous glucose tolerance test and suppressed postprandial hyperglucagonemia after mixed meal tolerance test. CONCLUSION: These results suggest that the combination of EXN and etanercept improve engraftment and long-term islet survival and function in subjects undergoing SI. This data, however, must be interpreted with some caution because of small sample size, lack of randomization, and sequential comparison with historical controls.

Islet transplantation with alemtuzumab induction and calcineurin-free maintenance immunosuppression results in improved short- and long-term outcomes.

BACKGROUND: Only a minority of islet transplant recipients maintain insulin independence at 5 years under the Edmonton protocol of immunosuppression. New immunosuppressive strategies are required to improve long-term outcomes. MATERIALS AND METHODS: Three subjects with unstable type 1 diabetes mellitus underwent islet transplantation with alemtuzumab induction and sirolimus-tacrolimus maintenance for 3 months and then sirolimus-mycophenolic acid maintenance thereafter. Follow-up was more than 2 years. Comparison was with 16 historical subjects transplanted under the Miami version of the Edmonton protocol. RESULTS: Insulin independence was achieved in 2 of 3 alemtuzumab and 14 of 16 historical subjects. Those who did not achieve insulin independence only received a single islet infusion. Insulin-independence rates remained unchanged in the alemtuzumab group, but decreased from 14 of 16 (88%) to 6 of 16 (38%) in the historical group over 2 years. Insulin requirements increased in the historical group while remaining stable in the alemtuzumab group. Comparison of functional measures at 3 months suggested better engraftment with alemtuzumab (P=NS). Further comparison of alemtuzumab versus historical groups, up to 24 months, demonstrated significantly better: Mixed meal stimulation index (24 months, 1.0+/-0.08 [n=3] vs. 0.5+/-0.06 pmol/mL [n=6], P<0.01), mixed meal peak C-peptide (24 months, 5.0+/-0.5 [n=3] vs. 3.1+/-0.3 nmol/mL [n=6], P<0.05), HbA1c (24 months, 5.4+/-0.15 [n=3] vs. 6.3+/-0.12 pmol/mL [n=10], P<0.01). Administration of alemtuzumab was well tolerated. There was no increased incidence of infections in alemtuzumab subjects despite profound, prolonged lymphocyte depletion. CONCLUSIONS: Islet transplantation with alemtuzumab induction was well tolerated and resulted in improved short- and long-term outcomes. Further investigation is underway for validation.

Effects of lung volume reduction surgery for emphysema on glycolipidic hormones.

BACKGROUND: Pulmonary emphysema is associated with cachexia and disregulation of the hormones regulating the glycolipid metabolism, insulin resistance, and altered substrate utilization. This study aimed at identifying the effects of lung volume reduction surgery (LVRS) on glycolipidic hormones compared to respiratory rehabilitation (RR). METHODS: Thirty-three patients with moderate-to-severe emphysema who were undergoing video-assisted thoracoscopic LVRS were compared to 31 similar patients who refused the operation and followed a standardized RR program. All patients were evaluated before and 12 months after treatment for respiratory function, body composition, glycolipidic hormones, metabolic parameters, and insulin resistance, which was calculated using the homeostatic model assessment index for insulin resistance (HOMA-IR). These groups were compared to a matched healthy control population. RESULTS: Only after LVRS significant improvements were obtained in respiratory function (FEV1, +25.2%; p<0.0001; residual volume, -19.5%; p<0.0001), metabolic parameters (total cholesterol, +13.1%; p<0.01; high-density lipoprotein cholesterol, +11.2%; p<0.01; triglycerides, +18.4; p<0.001; nonesterified fatty acid, -19.7%; p<0.001), and body composition (fat-free mass [FFM], +6.5%; p<0.01; fat mass [FM], +11.9%; p<0.01). The leptin/FM ratio (-6.1%; p<0.01) and resistin/FM ratio (-5.6%; p<0.01) decreased, whereas the adiponectin/FM ratio (+6.9%; p<0.01) and ghrelin (+9.2%; p<0.01) increased, together with reductions in glycemia (-8.8%; p<0.01), insulin level (-20.4%; p<0.001), and HOMA-IR (-27.2%; p<0.0001). The decrement in residual volume was correlated with increment of FFM (rho=-0.49; p<0.02), FM (rho=-0.55; p<0.009), and ghrelin (rho=-0.52; p<0.01), and also with decreases in leptin corrected for FM (rho=0.50; p<0.02) and, marginally, HOMA-IR (rho=0.35; p=0.07). CONCLUSIONS: After LVRS, glycolipidic hormone levels and nutritional status significantly improved, along with insulin resistance reduction and more physiologic utilization of substrates. Correlations between residual volume and body composition as well as glycolipidic hormone levels suggest that postoperative recovery in respiratory dynamics may induce favorable clinical changes when compared to RR.

Allosensitization of islet allograft recipients.

BACKGROUND: The immune monitoring of islet transplant recipients includes the assessment of panel reactive antibodies (PRA). A negative association of PRA+ with allogeneic solid organ graft survival has been recognized, but scattered data is available for islet transplantation. METHODS: We performed a retrospective analysis of PRA status in 66 patients with type 1 diabetes mellitus recipient of islet allografts between 1985 and 2006. RESULTS: Pretransplant PRA+ was observed in 10 subjects in the old trials and associated with kidney transplantation and/or pregnancies. Thirteen subjects displayed PRA+ at follow-up, eight of whom were de novo. Overall, PRA+ did not correlate with islet graft outcome: long-term graft survival was observed in the presence of basal or persistent PRA+ and graft dysfunction occurred also in the absence of PRA+. Loss of graft function was associated with PRA+ after lowering of immunosuppression or after infection episodes. Loss of C-peptide did not affect kidney graft function even in simultaneous islet-kidney transplant recipients. Mostly, PRA remained negative under adequate immunosuppression. Patients whose immunosuppression was discontinued invariably developed PRA+. CONCLUSIONS: Monitoring of PRA under immunosuppression may have little clinical value under adequate immunosuppression in islet transplant recipients. The implications of allosensitization after discontinuation of immunosuppression need to be evaluated to define the real clinical impact in this patient population.

New simple classification for operated bullous emphysema.

OBJECTIVES: Optimal results in bullectomy depend on both the size of the resected bulla volume and the reexpansion of the adjacent collapsed healthy pulmonary parenchyma. We hypothesized that the bigger the bulla is compared with residual volume, the greater are the possible benefits. We suggested a new prognostic classification according to bulla volume and its relationship with residual volume. METHODS: We retrospectively reviewed 121 patients with emphysematous bulla (>200 mL) who, from 1996 to 2006, underwent unilateral single (n = 64), unilateral multiple (n = 16), bilateral 1-stage (n = 9), and bilateral 2-stage (n = 32) bullectomies. Bulla volume and residual volume were measured by computed tomography and body plethysmography, respectively. Six-month postoperative decrement of residual volume values and their persistence below the baseline for 5 years were considered primary outcomes. Logistic regression was used to select significant variables. The receiver operating characteristic curve was used to identify the cutoff point for a possible classification system. RESULTS: There was no postoperative mortality. Significant postoperative improvements in respiratory function were found and correlated with bulla size. Residual volume improved in 75 patients (62%) and persisted in 20 patients (35% of the patients followed for > 5 years). Logistic regression selected bulla/residual volume ratio as the most predictive variable for both outcomes (P < .0001). The best cutoff individuated by the receiver operating characteristic curve analysis was 20% to achieve a high probability of residual volume improvement and 30% to minimize residual volume recurrence. CONCLUSIONS: Bullectomy provides good results, but more significant and long-lasting improvements are achievable with a greater ratio bulla/residual volume: scant for less than 20%, good but temporaneous for 20% to 30%, and good and long-lasting results for more than 30%.